Eyelid conditioning in rabbits is an unusually direct and experimentally tractable way to study learning and information processing of the cerebellum. Cerebellar patients experience debilitating motor impairments and damage of the lateral cerebellum contribute produces a variety of cognitive deficits. Understanding the internal operations of the cerebellum is therefore both important clinically, and important for the opportunity it provides to use an experimentally tractable system to the analysis of the neural basis of cognition. We propose to continue ongoing efforts that use eyelid conditioning to understand both what the cerebellum learning and computes and how its neurons and synapses accomplish underlie these capabilities. We will use high-density in vivo recordings of cerebellar neurons during the acquisition and execution of key behavioral properties of eyelid conditioning to test specific hypotheses derived from large-scale computer simulations of the cerebellum. We will use the ability to perform long-term recordings of cerebellar neurons to identify the sequence of events that occurs during learning of a new response and to quantify the relationships between cerebellar neurons and behavior. We will use lesions and in vivo recordings to examine how the contributions of cerebellar cortex to learning may vary depending on the timing of inputs to the cerebellum. These studies will help move our understanding of computation and learning in the cerebellum to a level not yet accomplished for any other system of the brain. PUBLIC HEALTH RELEVANCE: These experiments seek to understand the mechanisms of learning within the cerebellum. Understanding these mechanisms will help us understand how all systems of the brain support learning and memory. Such knowledge is the basis for the development of strategies to prevent and to treat the disorders of learning and memory that affect so many people.